drugs interaction & pharmacokinetic - associate professor ph.d. nguyen tuan dung

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TƯƠNG TÁC DƯỢ C ĐỘNG HỌC ( Pharmacokinetic drug interactions )

PGS.TS. Nguy ễn Tu ấ n Dũng

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Tạo phức chelat

The term chelation comes from the Greek word “chele” which means claw.

Tetracyclin Fluoquinolon

Carbidopa

Levodopa

MethyldopaLevothyroxin

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7

PHỨC CHELATE CỦA CÁC KHÁNG SINHVỚI KIM LOẠI ĐA HÓA TRỊ

( Tetracyclin, fluoquinolon )

7/21/2019 Drugs Interaction & Pharmacokinetic - Associate Professor Ph.D. Nguyen Tuan Dung

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9

FLUOROQUINOLON

Trước khidùng FQ

Sau khi dùngFQ

Moxifloxacin 8 4

Ciprofloxacin 6 2Gemifloxacin 3 2Levofloxacin 2 2Norfloxacin 2 2Ofloxacin 2 2Trovafloxacin 2 2

Thời điểm dùng các thuốc có chứa chất sắt

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11

012345

0 200 400

Time (min)

P l a s m a

L e v o d o p a

( n m o l / m

l )

ParkinsonSinemet (100/25)

levodopa & carbidopaferrous sulfate (325 mg)

Campbell NRC et al: Br J clin Pharmacol 30:599-605, 1990

FeSO4 và sự hấp thu c ủa Levodopa/Carbidopa

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PHÂN BỐ THUỐC

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PROTEIN(Albumin)

www

w

w

ww

w

PROTEIN(Albumin)

w

w

NSAID

NSAID

www

ww

w

Tương tác thuốc ở giai đoạn phân bố

CHUY ỂN HÓA THUỐC

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2014-12-6

CHUY ỂN HÓA THUỐC

• Levodopa• Warfarin• Statin• Ergotamin• Cafein

2014-12-6

CarbidopaFe B6

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BỆNH PARKINSON

Levodopa Carbidopa

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2014-12-6

Tác dụng phụ của levodopa

Chóng mặt,Buồn nôn, nôn,Khó ngủ,

Đau đầuNước tiểu, mồ hôi hoặc nước bọt : màu đỏ, nâu, hoặc đenBuồn ngủ đột nhiên xảy ra trong các hoạt động thường ngày

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38,762 Medicare dùng warfarin, cho th ấ y kháng n ấ m azole và một s ố nhóm kháng sinhcó th ể đưa đế n xu ấ t huy ế t trong vòng 2 tu ần (American Journal of Medicine, February 2012).

NGUY CƠ XUẤT HUY Ế T KHI PHỐI HỢ P WARFARIN VỚ I KHÁNG SINH

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28

C Y P 1A 2

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Ofloxacin 200 mg,Ciprofloxacin 250 mgEnoxacin 400 mg(all twice daily)

Caffeine(220 to 230 mg)

single doses

Inhibition ofcaffeine metabolism

Staib AH, - Interaction between quinolones and caffeine.--Drugs. 1987;34 Suppl 1:170-4.

CIPROFLOXACIN, ENOXACIN +OFLOXACIN -

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So sánh nồng độ trong huyết tương của DihydroergotaminDHE (2,5 mg) khi dùng riêng lẻ và khi kết hợp với TAO (2 g)

[Azria M. et al.J. Pharmacol, 1979]

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“ Ergotism ”

Necrosis of the extremities (gangrene)

“ERGOTISM”ADRAC ( Adverse Drug Reactions

Advisory Committee ) 12/2000

Phụ nữ 47 bị đau nửa đầu (migrain)

Erythromycin

Migral2 tay chân

N4 N5

Thí dụ 1

,

Clarithromycin

Erythromycin

Troleandomycin

Azithromycin

Dirithromycin

Australian Adverse Drug Reactions Bulletin, Vol 19, No 4

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THẢI TRỪ THUỐC

Bài tiết chủ động

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Gibaldi M., Int. J. Clin. Phar macol., 3, 1970

Penicillin amoxicillin, flucloxacillin,piperacillin + tazobactam

Cephalosporin cephalexin, cefazolin, cefuroxim,cefaclor, cefotaxim, ceftazidim

Quinolon Ciprofloxacin, norfloxacin

Probenecid

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TÁI HẤP THU THỤ ĐỘNG

Ion hóa(tan / nước)

Không ion hóa(tan / dầu)

pKa thuốcpH nước tiểu

Kiềm hóa nước tiểuAcid hóa nước tiểu

Thuốc acid yếu Thuốc kiềm yếu Thuốc acid yếu Thuốc kiềm yếu

Ion hóa(tan / nước)

Ion hóa(tan / nước)

Không ion hóa(tan / dầu)

Không ion hóa(tan / dầu)

Tái hấp thu Tái hấp thuThải trừ / nước tiểu

B. Urine pH

04

8

1216

20

4 5 6 7 8

Urine pH

S a l

i c y l i c a c i d r e n a

l

c l e a r a n c e

( m l / m i n )

Renal clearance of salicylate in 11 yo child with rheumatic fever treated with an antacid. Data fromLevy G, Lampman T, Kamath BL, Garrettson LK. Decreased serum salicylate concentrations inchildren with rheumatic fever treated with antacid.N Engl J Med 293:323-325, 1975.

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